Wednesday, August 31, 2011

Controlling by cooperating

Here's another example of cooperation in nature that was largely unexpected and is an installment in our  life-as-cooperation campaign.  An article by Voss et al., in the August issue of the journal Cell, describes the way potentially competing proteins actually cooperate to affect gene expression.

The genome contains protein coding sequences, but these are only a small percent of our DNA.  Another part of DNA consists of generally very short sequences in the vicinity of a protein-coding gene, that are used to control when (in which cells) the nearby gene is to be transcribed into messenger RNA and then translated into protein.  These regulatory DNA sequences work by being bound (grabbed physically) by proteins called transcription factors (TFs).  A TF is a protein whose physical and chemical properties make it bind (find and stick to) specific regulatory elements (REs) like (to make one up) CCTGCA.

The idea has been that such regulatory elements are bound by a specific TF and if that TF is itself being produced by the cell, it will grab the RE (stick to CCTGCA) and cause the gene to be transcribed.  If the TF isn't being produced by the cell, the CCTGCA remains naked and the gene inactive.

We're oversimplifying greatly, but this is the general idea.  But what if there is more than one TF that recognizes the same RE?  Then, our hyperDarwinian friends might presume that the two TFs compete to bind the sequence, with some sort of consequence for gene expression.  This would then set up an opportunity for natural selection to choose a winner, for example, so that the loser TF would lose its function.

But instead, as shown schematically in the figure, TF A, on the left, binds to a specific RE (the blue box along the black DNA line, which helps open up the wrapped-up DNA (called chromatin--black line of DNA wrapped around some packaging proteins represented by the pink ball) near a particular gene, that event allows another complex of proteins (the remodeling complex in the figure) to modify the DNA so that TF A gives way to enable TF  B to get access to the same RE sequence.  The nearby gene is expressed.

This is just one experimental example of a particular laboratory setting, rather than an analysis of such activities generally, so we don't know how pervasive such cooperation is.  The idea of intricate cooperation is to us only an additional instance of such a phenomenon, which we believe is far more pervasive and important to understand, in terms of biology, than competition.  Competition may, of course, help establish cooperative interactions if they are useful--and that would be the standard Darwinian theory.  But every day powerful molecular technologies are finding new examples of the kinds of extensive cooperative interaction that occurs between the passive sequence of DNA and the very dynamic activities of organisms.  Without such cooperation, we wouldn't be here to write these posts....and you wouldn't be here to read them!


Anonymous said...

In this example, I'm not convinced that "A" can actually be called a TF? Seems that it's role is to recruit the remodeling complex and make it possible for "B" to bind, but it's not initiating any transcription, in which case I don't feel "A" can be called a TF, but maybe a "pre-TF" or something of that nature. i.e., if A is just a necessary part of the cascade required for expression of the b gene, where's the opportunity for competition?

Ken Weiss said...

It's a good question, but perhaps one of definition. We're just reporting on a paper that we thought was interesting, and even that was just a specific example--and was touted by the editors in roughly the way we describe (as I remember).